System for conditioning surfaces in vivo

ABSTRACT

A system and method for conditioning surfaces of a body in vivo includes providing an electrical energy source, coupling the electric energy source to the surface, and delivering electropositive current from the electrical energy source to the surface so as to generate a sub-threshold current density on the surface. In preferred embodiments, the sub-threshold electropositive current density is between about 0.001 and about 1.0 mA/cm 2 .

RELATED APPLICATIONS

This application is a Continuation of and claims the benefit of U.S.patent application Ser. No. 11/402,463 filed Apr. 12, 2006, now allowed,the entire disclosure of which is herein incorporated by reference.

FIELD OF THE INVENTION

The present invention relates to systems and methods for conditioningvarious surfaces in vivo generally, and more particularly to systems andmethods for inhibiting blood platelet adhesion on such surfaces, andspecifically blood platelet adhesion to surfaces of implanted medicaldevices.

BACKGROUND OF THE INVENTION

Many surfaces in the human body that are exposed to blood flow are atrisk of blood component deposit formation thereon. Such deposits caninclude, for example, blood platelets, fibrinogen, minerals such ascalcium, and the like. Deposit formation on surfaces located at areas ofthe body which are critical to blood transmission can be detrimental oreven hazardous to the person's health. For example, deposit formation onheart valves, veins, and arteries can restrict the flow of bloodtherethrough and/or reduce the functionality thereof. As a result,deposit formation can lead to obstructed blood flow through at leastportions of the body, which limited blood flow can have serious negativeimplications on the health of the person.

A common form of coagulative deposition on surfaces within the body isthrombosis. This phenomenon is a result of cumulative blood componentadhesion to a surface, and can have a variety of causes. In some cases,thrombosis is believed to be caused by turbulence in the blood stream,with such turbulence causing relatively forceful impact among red bloodcells that causes damage to the cells, and ultimately proneness toadhere to surfaces.

While thrombosis can and does occur around native tissue surfaces, ithas been found that implanted medical devices often times act as focalpoints for thrombogenesis. Virtually all types of implanted medicaldevices bear some thrombogenic characteristics, in that the implantationof such devices typically alter to some extent the normal interaction ofblood flow at the implantation site. Some medical devices, however, havebeen found to be particularly susceptible to thrombogenesis. Artificialheart valves are an example of such implanted medical devices that bearrelatively significant thrombogenetic characteristics. While materialsand design for recently developed heart valves have reduced the risk ofthrombogenesis, patients receiving such artificial heart valvestypically are required to maintain an anti-coagulative drug protocol forthe remainder of their lives. Current anti-coagulative drug therapy isfar from ideal. Each patient with an implanted heart valve not onlycarries a risk for valve thrombosis or systemic emboli, but also a riskof bleeding which follows anti-coagulant therapy. Thromboemboli andhemorrhage comprise the majority of complications occurring in patientswith artificial heart valves.

It is therefore a principal object of the present invention to provide amethod for inhibiting thrombogenesis on a surface of a body in vivo witha reduced or eliminated need for anti-coagulant medication.

It is a further object of the present invention to provide a method forinhibiting thrombogenesis on the surface of a body in vivo by deliveringelectropositive current to such surface.

It is a still further object of the present invention to provide amethod for inhibiting blood component coagulation on a surface of animplanted medical device by delivering sub-threshold electropositivecurrent from an electrical energy source to the surface of the implantedmedical device.

It is a still further object of the present invention to inhibit bloodplatelet adhesion to a surface in vivo by coupling the surface to animplanted electrical energy source, wherein such electrical energysource provides an electropositive current density on the surface ofbetween about 0.001 and about 1 mA/cm² to the target surface.

SUMMARY OF THE INVENTION

By means of the present invention, thrombogenesis on one or moresurfaces of a body in vivo may be substantially inhibited without theaid of anticoagulant medication. Applicant has discovered that bloodplatelet adhesion to surfaces in vivo can be thwarted by applying asub-threshold electropositive current to such surfaces. A preferredrange of electropositive current density applied to target surfaces invivo is between about 0.001 and about 1 mA/cm².

In a particular embodiment, a method for inhibiting thrombogenesis on asurface of a body in vivo includes providing an electrical energysource, coupling the electrical energy source to the surface, anddelivering electropositive current from the electrical energy source tothe surface so as to generate an electropositive current density ofbetween about 0.001 and about 1 mA/cm² on the surface.

In preferred embodiments, the surface is electrically conductive, and insome cases is a portion of an implanted medical device.

In another embodiment, a method for inhibiting blood platelet adhesionto a surface in vivo includes applying electrical energy to the surface,with the electrical energy being derived from an electropositive currentproviding an electropositive current density of between about 0.001 andabout 1 mA/cm² on the surface.

A system for inhibiting thrombogenesis on a surface in vivo includes anelectrical energy source that is electrically coupled to the surface,with the electrical energy source providing electropositive currentdensity of between about 0.001 and about 1 mA/cm² on the surface.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram of a surface conditioning system of thepresent invention;

FIG. 2 is a magnified image of a clean pyrolytic carbon valve assembly;

FIG. 3 is a magnified image of a pyrolytic carbon valve assemblysubsequent to exposure to human blood; and

FIG. 4 is a magnified image of a pyrolytic carbon valve assemblysubsequent to exposure to human blood while being supplied withelectropositive current.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The objects and advantages enumerated above together with other objects,features, and advances represented by the present invention will now bepresented in terms of detailed embodiments described with reference tothe attached drawing figures which are intended to be representative ofvarious possible configurations of the invention. Other embodiments andaspects of the invention are recognized as being within the grasp ofthose having ordinary skill in the art.

With reference now to the drawing figures, and first to FIG. 1, a system10 of the present invention is preferably disposed in the human body,which location is identified by area 12. Although the components ofsystem 10 are illustrated in FIG. 1 as being in close proximity to oneanother, it is contemplated that such components may be disposed in adistributed fashion in the body. Due to the electrically coupled natureof the components of system 10, however, it is likely that mostembodiments of the invention involve component proximity that issufficiently close to enable electrical coupling through conventionalmeans.

In the embodiment illustrated in FIG. 1, system 10 includes anelectrical energy source 14, a medical device 16, and a return electrode18. In some embodiments of the invention, return electrode 18 isincorporated into the structure of electrical energy source 14, suchthat a separate electrode element 18 is not required. In preferredembodiments, electrical energy source 14 is electrically coupled tomedical device 16 through wire 20, and electrically coupled to electrode18 through wire 22. Other conventional mechanisms for electricallycoupling the components of system 10, however, are contemplated as beinguseful in the present invention. Depending upon the application, wire 20may be connected to medical device 16 in general, or may instead beconnected to medical device 16 at a specific location thereof, with thedistinction being which portion of medical device 16 is targeted forreceiving electrical current from electrical energy source 14. In manyembodiments, it is desired to deliver electrical current to medicaldevice 16 in its entirety. In some embodiments, however, it is desiredthat less than the entirety of medical device 16 receive electricalcurrent from electrical energy source 14. Such distinctions direct thelocation of where current should be allowed to travel in medical device16 from the wire connection point.

In an important aspect of the present invention, electrical energysource 14 preferably delivers electropositive current to medical device16 through an electrical coupling, such as electrically conductive wire20. The electropositive-biased current delivered to medical device 16preferably generates a sub-threshold current density on medical device16, in that the current density is below a threshold level required tostimulate adjacent tissue. Such a characteristic is particularlyimportant in applications wherein medical device 16 is disposed at oradjacent to cardiac tissue. Incidental excitation of cardiac tissuethrough an applied electrical current could result in undesiredcontraction of cardiac tissue, and, correspondingly, impaired cardiacfunctionality. Typically, threshold electrical current density forcardiac tissue is about 75 mA/cm². As such, system 10 of the presentinvention preferably generates no more than 1 mA/cm² current densityadjacent to cardiac tissue, so as to avoid undesired tissue excitation.Such a threshold level is also preferably utilized by system 10 of thepresent invention in non-cardiac applications, such that tissue adjacentto system 10 is not inadvertently excited.

In preferred embodiments, electrical energy source 14 delivers anelectropositive current to create an electropositive current density ofbetween about 0.001 and about 1 mA/cm² on the target surface. Such acurrent density range, however, may be broadened to other sub-thresholdcurrent densities, as required per application. In such cases,electropositive current density of somewhat greater than 1 mA/cm² may berequired for optimal blood platelet adhesion-inhibiting results.Applicant has determined, however, that an electropositive currentdensity of between about 0.001 and about 1 mA/cm² provides desirablelevels of blood platelet adhesion inhibition on target surfaces.

The arrangement of system 10 illustrated in FIG. 1 provides forelectropositive current delivery to medical device 16, due to the factthat electrode 18 acts as a “return” electrode to electrical energysource 14. Although the electropositive current may be delivered tomedical device 16 through a variety of modalities, a particularlypreferred mode of current transmission is in pulsatile format, whereinthe pulsatile current is in one of a variety waveforms. Such waveformsmay be, for example, sinusoidal, square, and triangular.

Electrical energy source 14 is preferably any device that is capable ofproducing and emitting electrical current from a designated location.Although electrical energy source 14 is illustrated in FIG. 1 as beingimplanted within body area 12, it is contemplated by the presentinvention that electrical energy source 14 may instead be placedextra-corporal while maintaining electrical coupling to a targetsurface, such as a surface of medical device 16. In some embodiments ofthe present invention, electrical energy source 14 is a commonlyimplanted electrical impulse device, such as a pacemaker ordefibrillator. Conventional pacemaker devices either include, or may bemodified to include, electrical leads to which wires 20, 22 may beconnected. In some embodiments, such pacemaker-type devices includeinternal “return” electrodes that negate the necessity of including aseparate electrode 18 in system 10. The arrangement illustrated in FIG.1, however, does in fact utilize such an electrode 18, which electrodemay be fabricated from, for example, titanium, and is preferablydisposed subcutaneously in the body.

While system 10 has been described above with reference to theembodiment illustrated in FIG. 1, a number of other applications for theelectropositive current generated by electrical energy source 14 arecontemplated by the present invention. In particular, the application ofsub-threshold electropositive current to a variety of surfaces isbelieved to be effective in inhibiting thrombogenesis thereon. Suchsurfaces, therefore, may include both native and non-native tissue, aswell as implanted medical devices. For example, electrical energy source14 may be electrically coupled to a native or non-native tissue heartvalve for inhibiting blood platelet adhesion thereto. Other native ornon-native tissue may also be conditioned through the system and methodof the present invention. Such tissues include, for example, arterialwalls, cardiac tissue, and the like. In other embodiments, electricalenergy source 14 may be electrically coupled to an implanted medicaldevice, such as medical device 16. A wide variety of implanted medicaldevices may be conditioned through the method and system of the presentinvention. Example implanted medical devices include mechanical heartvalves, stents, guide wires, implanted drug delivery ports, and thelike.

A particular aspect of the present invention is in the selectiveapplication of electropositive current to target surfaces. Such targetsurfaces may comprise any portion of a structure upon which the targetsurface resides. As such, the target surface that receives theelectropositive current may involve the entire structure, oralternatively, less than the entire structure. In the embodimentsillustrated in FIG. 1, medical device 16 may be wholly electricallyconductive, such that electrical current delivered to can 28 of device16 propagates to remaining elements thereof, such as valve leaflets 30,32 thereof. In other embodiments, however, it may be desired that onlyvalve leaflets 30, 32 of medical device 16 receive electropositivecurrent, such that wire 20 is connected to a position of medical device16 that is in electrical continuity with, for example, valve leaflets30, 32, but electrically insulated from, for example, can 28. Inpreferred embodiments, therefore, the target surface to which electricalenergy source 14 is electrically coupled is electrically conductive, soas to most efficiently transmit the electropositive current thereacross.The efficient transmission of electrical current throughout the targetsurface effectuates a high level of conditioning/treatment in inhibitingthrombogenesis thereon.

The following examples set forth specific conditions under whichbeneficial results of the system and method of the present inventionhave been observed. The examples provided hereinbelow, however, shouldnot be construed to limit the scope of the invention to the specificoperating conditions set forth therein.

Control

A pyrolytic carbon aortic valve assembly manufactured by ATS Medical,Inc. of Plymouth, Minn. as Model #500FA-25 having a surface area of12.42 cm² was cleaned by wiping with ethyl alcohol and subsequent airdrying for ten minutes. The cleaned pyrolytic valve assembly wasinspected under a scanning electron microscope at a magnification of1000×. A photograph from such inspection is shown in FIG. 2.

Example I

A pyrolytic carbon aortic valve assembly similar to that utilized in thecontrol was cleaned as described with reference to the controlprocedure. The pyrolytic carbon valve assembly was exposed to a first200 ml aliquot of a human blood sample for 45 min. at 37° C. in apulsatile blood perfusion system. The blood perfusion system wasarranged with an approximate output of 5 L per min. The valve leafletsof the assembly were oriented in the blood perfusion system with theirrespective major planes disposed parallel to axial blood flow throughthe system. Subsequent to the exposure to the human blood, the pyrolyticcarbon valve assembly was removed from the system, rinsed in saline, andinspected under scanning electron microscope at a magnification of1,000×, with an image from such inspection being shown in FIG. 3. Theimage illustrates completely confluent blood platelet adhesion.

Example II

A pyrolytic carbon valve assembly similar to those utilized in thecontrol and in Example I was cleaned through the protocol identified inthe control. The cleaned pyrolytic carbon valve assembly was exposed toa second 200 mL aliquot of the human blood sample for 45 min. at 37° C.in a pulsatile blood perfusion system. The blood perfusion system wasset up with an approximate output of 5 L per min. An electrical lead waselectrically connected to the valve assembly carrying a current of 3.0mA to create electropositive current density of 0.24 mA/cm² at the valveassembly. The current was delivered as a pulsed square waveform having a25 ms duration pulse at 20 Hz. The valve leaflets were axially orientedin the blood perfusion system, such that the major planes of therespective valve leaflets were parallel to the direction of blood flow.

Upon completion of 45 min. of exposure to the blood perfusion system,the valve assembly was removed from the system, rinsed in saline, andexamined under a scanning electron microscope at a magnification of1000×. The image from such examination is shown in FIG. 4. Asillustrated therein, very little platelet adhesion is observed. Such aresult shows clear improvement over the blood platelet adhesion levelsobserved in Example I. Accordingly, the application of 0.24 mA/cm² ofelectropositive current density to the valve assembly significantlyinhibited blood platelet adhesion thereon.

The invention has been described herein in considerable detail in orderto comply with the patent statutes, and to provide those skilled in theart with the information needed to apply the novel principles and toconstruct and use embodiments of the invention as required. However, itis to be understood that the invention can be carried out byspecifically different devices and that various modifications can beaccomplished without departing from the scope of the invention itself.

What is claimed is:
 1. A medical device comprising: a blood contactingsurface having an electropositive current density of between about 0.001and about 1.0 mA/cm²; wherein the blood contacting surface inhibitsthrombogenesis.
 2. The medical device of claim 1 wherein the medicaldevice is an implantable medical device.
 3. The medical device of claim1 wherein the medical device is a prosthetic heart valve.
 4. The medicaldevice of claim 1 wherein the blood contacting surface is a valveleaflet.
 5. The medical device of claim 1 wherein the medical device isa stent.
 6. The medical device of claim 1 wherein the blood contactingsurface inhibits blood platelet adhesion.
 7. The medical device of claim1 further comprising an electrical energy source delivering betweenabout 0.1 and about 10 mA electropositive current to the bloodcontacting surface.
 8. The medical device of claim 7 wherein theelectrical energy source is an implantable electrical energy source. 9.The medical device of claim 7 wherein the electrical energy source is anextra-corporal electrical energy source.